Abstract
BackgroundLong non-coding RNAs (lncRNA) have an essential role in progression and chemoresistance of hepatocellular carcinoma (HCC). In-depth study of specific regulatory mechanisms is of great value in providing potential therapeutic targets. The present study aimed to explore the regulatory functions and mechanisms of lncRNA TINCR in HCC progression and oxaliplatin response.MethodsThe expression of TINCR in HCC tissues and cell lines was detected by quantitative reverse transcription PCR (qRT-PCR). Cell proliferation, migration, invasion, and chemosensitivity were evaluated by cell counting kit 8 (CCK8), colony formation, transwell, and apoptosis assays. Luciferase reporter assays and RNA pulldown were used to identify the interaction between TINCR and ST6 beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1) via miR-195-3p. The corresponding functions were verified in the complementation test and in vivo animal experiment.ResultsTINCR was upregulated in HCC and associated with poor patient prognosis. Silencing TINCR inhibited HCC proliferation, migration, invasion, and oxaliplatin resistance while overexpressing TINCR showed opposite above-mentioned functions. Mechanistically, TINCR acted as a competing endogenous (ceRNA) to sponge miR-195-3p, relieving its repression on ST6GAL1, and activated nuclear factor kappa B (NF-κB) signaling. The mouse xenograft experiment further verified that knockdown TINCR attenuated tumor progression and oxaliplatin resistance in vivo.ConclusionsOur finding indicated that there existed a TINCR/miR-195-3p/ST6GAL1/NF-κB signaling regulatory axis that regulated tumor progression and oxaliplatin resistance, which might be exploited for anticancer therapy in HCC.
Highlights
Hepatocellular carcinoma (HCC), the most common type of liver malignancies, is the third leading cause of cancer-related deaths worldwide [1]
The opposite effect was verified in hepatocellular carcinoma (HCC) cells with overexpression (Fig. 3E-H; Fig. S1D, all P < 0.05). These findings indicated that Terminal differentiation-induced non-coding RNA (TINCR) acts as an oncogenic Long non-coding RNAs (lncRNA) to promote proliferation, invasion, and migration, and induces sensitivity to oxaliplatin in HCC
TINCR acts as a competing endogenous RNA (ceRNA) and competitively absorbs miR‐195‐3p To figure out the underlying regulatory mechanism, we firstly explored the predictive location of TINCR in LncLocator
Summary
Hepatocellular carcinoma (HCC), the most common type of liver malignancies, is the third leading cause of cancer-related deaths worldwide [1]. A-B, TINCR expression in HepG2 and HuH7 cells transfected with si-TINCRs or scrambled control (A), and pcDNA3.1-TINCR or empty vector (B). C-D, CCK-8 assay of HepG2 and HuH7 cells transfected with si-TINCRs or scrambled control (C), and pcDNA3.1-TINCR or empty vector (D). E-F, Representative images (left) and quantification (right) of the colony formation assay in HepG2 and HuH7 cells transfected with si-TINCRs or scrambled control (E), and pcDNA3.1-TINCR or empty vector (F). G-H, Representative images (left) and quantification (right) of transwell migration and invasion assays in HepG2 and HuH7 cells transfected with si-TINCRs or scrambled control (G), and pcDNA3.1-TINCR or empty vector (H). Long non-coding RNAs (lncRNA) have an essential role in progression and chemoresistance of hepatocellular carcinoma (HCC). The present study aimed to explore the regulatory functions and mechanisms of lncRNA TINCR in HCC progression and oxaliplatin response
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